Hemoglobin Biochemical and Molecular Properties Research (Term Paper Sample)

Hemoglobin biochemical and molecular properties
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Hemoglobin term paper
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Abstract
Red blood cells are important for transfer of respiratory gases. It helps in maintaining constant body metabolism by ensuring supply of oxygen for aerobic respiration. Proper maintenance of gases concentration in the blood helps in maintaining optimum conditions for normal body activities. Red blood cells have hemoglobin that function to transport oxygen from lung to other body parts and transports carbon dioxide to the lungs for excretion. Hemoglobin has four subunits, each subunit contains heme group that contains iron atom, which bind single oxygen molecule. Hemoglobin has four heme groups therefore; one hemoglobin can transport four oxygen molecules. Hemoglobin undergoes conformational change to either bind or release oxygen. Exchange of gases in body tissues take place along the blood capillaries. Positive effector molecules like oxygen increases affinity of hemoglobin to oxygen in lungs by changing conformation from tense to relaxed state. Actively metabolizing cells produce wastes such as carbon dioxide and hydrogen ions that act as negative effectors. These negative effector molecules promote release of oxygen molecules from hemoglobin. Abnormal production of hemoglobin can result in anemia. Therefore, it is important to understand molecular structure of hemoglobin as it is major transport agent of respiratory gases.
Introduction
Hemoglobin is protein contained in red blood cells responsible for transfer of oxygen from lungs to other body parts. It is composed of four polypeptide chains; 2α and 2β chains and has a relative molecular weight of 64, 500 kilodaltons. Each α and β polypeptide chain is made up of 141 and 146 amino acids respectively. Each subunit has heme binding pocket therefore there are four heme per single molecule of hemoglobin (Lugin et al., 2003). Each heme binds to single molecule of oxygen enabling transfer of four molecules of oxygen when hemoglobin is fully packed. Heme part of hemoglobin is synthesized in mitochondria while protein parts (globin) are synthesized in the cytosol by ribosomes. Heme group consist of protoporphyrin which is made up of four pyrrole rings surrounding iron at the center. Iron of normal hemoglobin exists in ferrous state (Fe+) while oxidation of Fe+2 to Fe+3 form methemoglobin which does not bind oxygen.
Hemoglobin binds to oxygen in lungs to form oxyhemoglobin that is transported systemic arteries to distal organs and tissues. Upon reaching tissue cells hemoglobin dissociates and releases oxygen to form deoxyheamoglobin and travels back via pulmonary veins to pick oxygen in the lungs. It is interesting to note that hemoglobin concentration in blood varies with age and gender. Male generally have high hemoglobin concentration (135-172 g/l) compared to females (120-162 g/l) as they are masculine requiring more oxygen. Abnormal hemoglobin results in conditions like sickle cell anemia and thalassemia. Sickle cell anemia results from incorrect amino acid sequences whereas thalassemia results from reduced or no production of one or more globin chains.
Carbon monoxide has high affinity for oxygen as compared to hemoglobin accounting for high toxicity of CO. Cooley’s anemia arises from excess β chains due to overproduction causing precipitation and results in cell hemolysis (Capalleni et al., 2005). All these abnormalities results in low oxygen delivery to body tissue resulting in tissue hypoxia. Brain is sensitive to low oxygen supply and is fatal causing cardiac failure. Sideropenic anemia result from insufficient FE+2 in the body where as sickle cell anemia is as a result of point mutation causing substitution of glutamine for valine. Anemia results in overall retarded growth and splenomegaly. Impaired hemoglobin synthesis results in accumulation of heme precursors in the blood as aminolevulinic acid that is excreted in urine causing lead poisoning (Needleman, 2004). Hemoglobin is therefore one of the most basic protein needed for survival of an organism. This is because every cell except muscle cells depends on hemoglobin for oxygen supply. Abnormality in its production results in devastating effects forming basis of the current study about the protein.
Figure SEQ Figure \* ARABIC 1: Structure of porphyrin
Regulation of the protein
Hemoglobin exists in two conformational states: relaxed (R) and Tense (T). Relaxed state occurs when hemoglobin is oxygenated while tense state arises from deoxygenation. R and T states are stable in presence and absence of oxygen respectively. Binding of oxygen to R hemoglobin results in rearrangement of electrons within ferrous iron to compact Fe+2 to fit plane of porphyrin. This structural change causes whole hemoglobin subunit to undergo conformational leading to transition from T to R state. The α1β1 and α2β2 dimers of hemoglobin rearrange and rotate approximately 15 degrees with respect to each other. Binding of single oxygen molecule to hemoglobin causes conformation change that result in increased affinity for oxygen to the unbound sites. Therefore, as more oxygen binds to one of the oxygen binding sites, affinity for remaining sites increases as compared to previous. The fourth oxygen-binding site has highest affinity when hemoglobin is bound to three oxygen molecules. Oxyhemoglobin upon reaching cell tissues dissociates to release oxygen to cells. Low oxygen concentration in tissue cells as compared to arterial blood causes concentration gradient triggering dissociation of oxyhemoglobin to release oxygen. Similarly, dissociation of one of the four bound oxygen molecules results in the dissociation of the remaining three at a sequentially faster rate.
Allosteric regulation occurs when effectors bind to hemoglobin. Positive effectors increase oxygen-binding affinity of hemoglobin. Oxygen is an example of positive effectors as binding of one oxygen molecule increases affinity of oxygen to the remaining sites. Carbon dioxide is a negative effector that reduces oxygen-binding affinity. Binding of CO2 to oxyhemoglobin on the N-terminal end causes formation of carbamate groups that causes conformational change to stabilize T state of deoxyhemoglobin. Metabolically active cells deficient of oxygen produce a lot of CO2 to promote dissociation of oxyhemoglobin to release oxygen. Physico-chemical properties such as pH and temperature regulate saturation of hemoglobin with oxygen. Alkaline pH favors stabilization of R conformation in the lungs. On the other hand, acidic pH and an increase in temperature and 3-biphospoglutamate favor stabilization of T conformation in distal organs.
Long-term regulation of hemoglobin is through control of its synthesis. 5-aminolevulinice acid (ALA) synthase enzyme control rate limiting step in hemoglobin synthesis (Ponka, 1999). It catalyses formation of 5-aminolevulinice acid in the liver. An increase in amount of ALA synthase results in production of more heme leading to higher concentration of hemoglobin. ALA synthase is inhibited by heme through feedback inhibition mechanisms. In addition, availability of iron regulates rate at which heme is synthesized. Low iron concentration result in low heme formation resulting in anemia.
Metabolic functions of hemoglobin
Hemoglobin helps to transport oxygen from lungs to various parts of the body. Oxygen in the lung is at higher concentration than in the blood. Oxygen therefore binds to hemoglobin to form oxyheamoglobin, which transport oxygen to peripheral organs. Hemoglobin in red blood cells has high affinity for oxygen thus ensuring they are saturated with oxygen before they leave lungs to other body parts. Cooperativity regulation is observed in hemoglobin as the affinity of unbound oxygen sites increases with the binding of more oxygen. Reactions in the lungs occur as shown below:
Red blood cells releases oxygen to body tissues whereby oxyhemoglobin is dissociated to deoxyhemoglobin plus oxygen. Hypoxia cell tissues create concentration gradient favoring release of oxygen by hemoglobin. Red blood cells transport small percentage of carbon dioxide bound to surface of hemoglobin. The reaction summarizing dissociation of oxygen in peripheral tissues is summarized below:
Figure SEQ Figure \* ARABIC 2: images showing exchange of respiratory in body tissues (a) and in the lungs (b)
Source: https://www2.estrellamountain.edu/faculty/farabee/BIOBK/BioBookRESPSYS.html
Cellular and physiological processes impacted by hemoglobin
Aerobic respiration is the major metabolic process which occurs in cell’s mitochondria and depends entirely on presence of oxygen. Efficient delivery of oxygen to tissues depends on formation of normal hemoglobin. Hypoxia in cells when detected stimulate cascade of events to increase hemoglobin concentration. Under low hemoglobin concentration, the body tissues are starved of oxygen and are forced to lower metabolic reactions. Inadequate supply of oxygen to mitochondria triggers formation of reactive species of oxygen that causes cell death (Turrens, 2003). The brain must be supplied with enough oxygen therefore more blood is channeled towards the brain at expense of other organs when hemoglobin concentration in the blood is low. Low number of hemoglobin in blood reduces oxygen binding sites thus decreasing oxygen supply to actively metabolizing cells. Some cells may switch to anaerobic respiration producing lactic acid causing blood acidosis (Zoll et al., 2002). Anaerobic respiration produce less energy compared to aerobic causing muscle fatigue.
Potential implication of hemoglobin in human health
Normal heme has iron in reduced state (Fe+2). However, ferrous iron when oxidized to ferric (Fe+3) in normal hemoglobin forms methemoglobin that ...